According to Celena Haas (Caesars Palace Director of Public Relations), the suite the characters stayed at was modeled after two of the resort's luxurious suites in its Forum Tower: a well-appointed penthouse and the so-called "Rain Man suite," located on the 68th and 69th floors of the Forum Tower.
Bradley Cooper's character, Phil, is an English teacher. The book he is teaching can be seen on his desk: Of Mice and Men by John Steinbeck.
Due to the physicality of his role, Ed Helms lost a reported 8lbs in weight.
When Zach Galifianakis (Alan) makes the joke about him not being allowed near schools or a Chuck E. Cheese, that is a direct reference to one of his staple jokes in his stand up: "When you look like I do, it's hard to get a table for one at Chuck E. Cheese."
Plans for a sequel had already been made before this film was even in theaters.
During the first scene involving Las Vegas, the Danzig song "Thirteen" is played. The room number the characters stay in is room "2452", which added together separately equals "13". Thirteen is a very unlucky number in Las Vegas, hence the movie's entire plot.
Three sets of twins and a dummy were used to portray the baby.
Bradley Cooper and Justin Bartha's third film together, after Failure to Launch (2006) and New York, I Love You (2009).
Lindsay Lohan was offered the part of the stripper, Jade, but turned it down. She did not like the script and thought the movie would bomb. Heather Graham was given the role instead. Lohan later admitted to regretting the decision.
No effects or prosthetics were created for Stu's missing tooth. Actor Ed Helms never had an adult incisor grow, and his fake incisor was taken out for the parts of filming where Stu's tooth is missing.
One of the songs from the movie is "Can't Tell Me Nothing" by Kanye West. One of the stars, Zach Galifianakis was actually paid by West to make an alternative music video for the song.
During filming in Las Vegas, one of the Mercedes (a very beat up and distinctive one) was stolen from the lot where the vehicles were being kept. The next day the production was filming driving sequences and traffic was being held up by the local police. A production person noticed that a very distinctive Mercedes was part of the cars being held, the police were told, the driver was arrested and the car was recovered.